SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise

• Main Authors: Teppei Fujikawa, Carlos M Castorena, Mackenzie Pearson, Christine M Kusminski, Newaz Ahmed, Pavan K Battiprolu, Ki Woo Kim, Syann Lee, Joseph A Hill, Philipp E Scherer, William L Holland, Joel K Elmquist
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2016-11-01
• Series: eLife
• Subjects: hypothalamus; metabolism; exercise; VMH; SF-1; Nr5a1
• Online Access: https://elifesciences.org/articles/18206

Exercise has numerous beneficial metabolic effects. The central nervous system (CNS) is critical for regulating energy balance and coordinating whole body metabolism. However, a role for the CNS in the regulation of metabolism in the context of the exercise remains less clear. Here, using genetically engineered mice we assessed the requirement of steroidogenic factor-1 (SF-1) expression in neurons of the ventromedial hypothalamic nucleus (VMH) in mediating the beneficial effects of exercise on metabolism. We found that VMH-specific deletion of SF-1 blunts (a) the reductions in fat mass, (b) improvements in glycemia, and (c) increases in energy expenditure that are associated with exercise training. Unexpectedly, we found that SF-1 deletion in the VMH attenuates metabolic responses of skeletal muscle to exercise, including induction of PGC-1α expression. Collectively, this evidence suggests that SF-1 expression in VMH neurons is required for the beneficial effects of exercise on metabolism.